Traumatic brain injury, cerebral ischemia, metabolic insults such as glucose deprivation and oxidative stress as well as neurodegenerative disorders can cause permanent neurological damage and are a major cause of mortality and morbidity. Neuronal damage, leading to acutely injured or degenerating neurons, can also result from aberrant, excessive stimulation of neurons through excitatory neurotransmitters (excitotoxicity), in particular by the excitatory neurotransmitter glutamate.
Neuroprotective factors such as the nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, novel neurotrophin-1 or insulin-like growth factor 1 (IGF-1) play an important role in the maturation, function, repair and survival of neurons (Sofroniew et al., 2001). Neuronal expression of neuroprotective factors has been found to be markedly upregulated following seizures, cerebral ischemia and other brain injuries, initiating a cascade of events in neurons and surrounding glia cells to prevent further brain damage.
The knowledge about neuroprotective factors has to date not translated into effective treatments following neuronal insults and, as a result, current therapies for traumatic brain injury, ischemic stroke and neurodegenerative disorders are inadequate and not sufficient to stop neuronal cell loss and death. It would, therefore, be highly desirable to have therapeutic agents available for immediate treatment following brain injuries or even prior to brain injuries to mitigate or to prevent neuronal cell death.